Deciphering the Mechanisms and Targets of Compound Houttuynia Cordata Mixture in COVID-19 Prevention through Integrated Network Pharmacology and Experimental Verification.

Abstract

In December 2019, a novel coronavirus, subsequently named COVID-19, emerged and rapidly propagated both within China and globally. Although the Compound Houttuynia Cordata Mixture (CHM), a traditional Chinese medicine, has shown clinical efficacy in preventing and treating COVID-19, its underlying mechanisms remain inadequately understood. This study evaluates the effectiveness and explores the potential mechanisms of CHM against COVID-19 through the application of network pharmacology, molecular docking, and pseudovirus entry assays. Theoretical analyses based on meridian tropism principles suggest that CHM primarily targets the lung meridian, with additional effects on the heart, stomach, and other organs. An initial review of the TCMSP and STITCH databases identified 103 active components and 205 putative targets, with 69 targets considered therapeutic for COVID-19. Further examination of the GSE152586 dataset, in conjunction with previously identified targets, revealed 16 hub targets potentially critical for CHM's therapeutic effects in vivo. These hub genes are mainly associated with immune responses, inflammation, and cellular responses to external stimuli. Additionally, 59 compounds were identified, including pivotal components such as quercetin, baicalin, and luteolin, which play central roles in the drugs-compounds-targets network. At the cellular level, CHM significantly inhibited the LPS-induced secretion of IL-6 and IL-1β, and curtailed pseudovirus invasion of cells. This comprehensive study elucidates the potential mechanisms and targets of CHM in the prevention of COVID-19, thereby providing a solid foundation for further clinical research.